Contribution of inorganic arsenic sources to population exposure risk on a regional scale.

Chronic exposure to inorganic arsenic (iAs) in the human population is associated with various internal cancers and other adverse outcomes. The purpose of this study was to estimate a population-scale exposure risk attributable to iAs consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK) model and biomonitoring data of iAs in urine. The urinary As concentrations were obtained from a total of 1,043 subjects living in an industrial area of Taiwan. The results showed that the study subjects had an iAs exposure risk of 27 % (the daily iAs intake for 27 % study subjects exceeded the WHO-recommended value, 2.1 µg iAs day(-1) kg(-1) body weight). Moreover, drinking water and cooked rice contributed to the iAs exposure risk by 10 and 41 %, respectively. The predicted risks in the current study were 4.82, 27.21, 34.69, and 64.17 %, respectively, among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh reported in the literature. In conclusion, we developed a population-scale-based risk model that covered the broad range of iAS exposure by integrating stochastic PBPK modeling and reverse dosimetry to generate probabilistic distribution of As intake corresponding to urinary As measured from the cohort study. The model can also be updated as new urinary As information becomes available.

Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions.

In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 µg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 µg m(-3)) and Western (21.47 ± 11.44 µg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 µg m(-3)), followed by Western (0.86 ± 1.43 µg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 µg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6).

Hypertension incidence after tap-water implementation: a 13-year follow-up study in the arseniasis-endemic area of southwestern Taiwan.

Hypertension is the leading cause of cardiovascular disease worldwide. Long-term arsenic exposure has been linked to increased risk for hypertension; however, little is known whether a previous exposure has lingering effects on hypertension after the exposure being reduced significantly for decades. The study cohort was established in 1990 in an arseniasis-endemic area of 3 villages - Homei, Fuhsin, and Hsinming in Putai Township located on the southwestern coast of Taiwan, where residents were exposed to artesian well water (median level=700 to 930 µg/L) until early 1970s. The original cohort consisted of 490 non-hypertensive residents over 30-yrs-old and 352 of them were successfully followed up in 2002/03. Arsenic concentrations in the artesian well water consumed by residents during 1960s were used to indicate the previous exposure while urinary arsenic species measured in 2002/3 was used to represent current exposure. Hypertension incidences were 27.4, 65.6, and 69.1, per 1000 person-years for men aged 35-49, 50-64, and 65-74 years, respectively being higher than the corresponding rates of 25.1, 46.1, and 57.2 in a community-based longitudinal study. Cancer was the major cause of the total deaths (17/30=57%). Diastolic blood pressure was shown to increase with an increased cumulative arsenic ingestion from drinking water (ß=0.27, p<0.001). The incidence was increased by 2.43-fold in subjects of As(V)≥2.67 µg/g creatinine as compared to those of As(V)<1.20 µg/g creatinine (the third vs. first tertile; p=0.047) after adjustment for conventional risk factors. This study suggests that three decades after cessation of drinking artesian well water, residents of the endemic area are still at increased risk for developing hypertension, particularly those who excrete high amounts of As(V).

The association between total urinary arsenic concentration and renal dysfunction in a community-based population from central Taiwan.

Arsenic (As) is an important environmental toxicant that can cause cancer and cardiovascular disease, but the relationship between As exposure and renal dysfunction is not clear. The aim of this study is to examine the association between As exposure and renal dysfunction in a community-based population in central Taiwan. One thousand and forty-three subjects were recruited between 2002 and 2005. The risk for type 2 diabetes was increased by 2-fold (p<0.05) in subjects with total urinary As (U-As)>75 µg g(-1) creatinine as compared with subjects whose U-As was ≤ 35 µg g(-1) creatinine after the adjustment for potential confounders. The adjusted odds ratio for an abnormal ß2 microglobulin (B2MG>0.154 mg L(-1)) was significantly higher in subjects with U-As>35 µg g(-1) creatinine as compared with the reference group adjusted for age, sex, living area, cigarette smoking, diabetes, and hypertension. The risk for abnormal B2MG and estimated glomerular filtration rate (eGFR<90 mL min(-1)(1.73 m(2))(-1)) was both increased around 2-fold (p<0.05) in subjects with U-As>75 µg g(-1) creatinine as compared with those with U-As ≤ 35 µg g(-1) creatinine adjusted for all the risk factors plus lead (Pb), cadmium and nickel. The prevalence of abnormal B2MG was 4.82 times higher in subjects with both over the median levels of U-As (85.1 µg L(-1)) and urinary Pb (18.9 µg L(-1)) as compared to both lower than the median (p<0.001). These results indicate that U-As might relate to renal dysfunction even other important risk factors were taken into account. Follow-up studies for causal inference are warranted.

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-alpha-induced vascular endothelial dysfunction.

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-alpha)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-alpha induces various biological effects on vascular cells, TNF-alpha dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-alpha concentrations, we adopted the lower TNF-alpha (0.2 ng/ml) to rule out the possible involvement of other TNF-alpha-induced biological effects. Inhibition of glutathione synthesis by l-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-alpha-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-alpha-induced nuclear factor-kappaB (NF-kappaB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-alpha. Inhibition of ERK, JNK, or NF-kappaB attenuates TNF-alpha-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-alpha induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-kappaB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-alpha. Although AP-1 activation by the lower TNF-alpha was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-alpha-induced adhesion molecule expression.

Body burden of dioxins and dioxin-like polychlorinated biphenyls in pregnant women residing in a contaminated area.

A large pentachlorophenol (PCP)-manufacturing plant located in southwestern Taiwan operated between 1965 and 1982. The present study was conducted to ascertain whether an increased body burden of dioxins existed in pregnant women living in an area of Tainan city contaminated by chemicals from this plant. Twenty-eight pregnant subjects, 21-39 years of age and residing in the study area between March and December of 2004 with a mean dwelling time of 6.07+/-6.11 years, were recruited. Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (PCBs) in serum of recruited residents were determined. Pregnant women residing in the study area >3 years had significantly higher PCDD (7.48 versus 5.13 pg-toxic equivalents [TEQ]/g-lipid) and dioxin-like PCB (6.70 versus 3.74 pg-TEQ/g-lipid) values as compared to those residing < or = 3 years. Furthermore, dioxin concentrations increased with increasing dwelling time. Statistical analyses performed according to demographic characteristics and socioeconomic and dietary habits revealed that total TEQ values were significantly associated with fish consumption and smoking status. Dioxin congeners with greater degrees of chlorine substitution (e.g., HpCDD/F and OCDD/F) partitioned to greater degrees in the subjects of this study as compared to subjects in the general Taiwanese population. The findings of this study strongly implicate the activity of the PCP manufacturing plant in the observed increase in dioxin body burden. Investigation of the health consequences of this increased body burden is recommended.